The present invention belongs to the field of equipment for reduction and prevention of obesity, and improvement of obesity for health and beauty, especially relating to ultrasound equipment for medical treatment and prevention of obesity and improvement of obesity for health and beauty.
Recently adult (including Mammalian) diseases such as diabetes mellitus, hypertension, and vascular degeneration of brain and viscera have become serious problems. Their greatest origin is obesity.
For improvement of obesity, it is known scientifically that suppression of caloric intake and exercise are effective. Administration of appetite suppressers and digestion/intake suppressers in addition to thermo-metabolism enhancers are under study and some of them are approved by the Government.
As for exercise, persons tend to undertake dieting, walking, physical exercise, dancing, swimming, cycling, etc, due to a shortage of exercise resulting from sedentary occupations and the popularization of automobiles. However, it is a big problem that maintaining an exercise program is very difficult without ample time and strong will. Therefore, a method for reducing obesity comfortably and effectively is desired.
There are some aesthetic salons in the market which are announcing fat reduction by ultrasound as a variation of folk medicine. But such techniques have no scientific evidence, the used frequency of all the equipment is 1 MHz, and there is no display of acoustic intensity, but only an electric input power per transducer unit area. For example, the book titled xe2x80x9cWrinkles Stretched in only 5 min.xe2x80x9d by Masuda, published on Aug. 25, 1996 by Success Marketing Co. Ltd. discloses an ultrasound treatment method using an ultrasound applicator for beauty, increased blood flow and lymphoid flow, by the effect of thermo-heating and massage, for enhancing beauty of the skin. Such thermo-heating brings the fat to an easily decomposable state and massage further promotes such decomposing. Stimulation, by ultrasound, of the sensitive spot known as xe2x80x9ctubo in acupuncture and moxibustion is also disclosed. In the aforesaid book, 1-10 MHz for medical treatment and 1 MHz for beauty enhancement are disclosed. In relation to the sonicating acoustic power density, or intensity, the following facts are disclosed: The safety limit defined by the Society for Ultrasound for Medicine and Biology is 1000 mW/cm2 for continuous wave (CW) sonication and 240 mW/cm2 (SPTA) for pulse wave (PW) sonication. For beauty enhancing applications, the intensity used was 1500-2000 mW/cm2 for thick muscles, 1000-1500 mW/cm2 for thin muscles, 500 mW/cm2 for the face in CW sonication and 120 mW/cm2 for the face in PW sonication. And their level is half of the aforesaid safety limit.
However, the intensity used for the thick and thin muscles disclosed above clearly exceeds the safety limit of 1000 mW/cm2 for CW, so the disclosed intensity must be the electric power per transducer unit area. If we assume they are of electric power intensity, then an electric intensity of 1500-2000 mW/cm2 corresponds to 500-700 mW/cm2 of acoustic intensity, as the electric to acoustic conversion efficiency of the transducer is usually 30% and coincides with the description that they are half the safety limit. In another chapter it is disclosed that a scientific experiment on reduction of fat was carried out and the reduction was effective, and a reduction amount is reported. Although a scientific description of the sonication conditions such as intensity is not shown, it is reasonably presumed in context with the nearby sentences that 1 MHz of the equipment for beauty enhancement was used, and that its acoustic intensity was less than 700 mW/cm2 again considering the aforesaid electric to acoustic conversion efficiency.
Concerning patent applications, Tokukai Hei-4-89058 (Yahmann Co) discloses an equipment for beauty using a frequency of 1-3 MHz and an intensity of 100-500 mW/cm2. Tokukai Hei 3-123559 (Yahmann Co.) discloses a fat reducing effect which is introduced by muscle shrinkage and an improvement in blood /lymphoid liquid flow. In the detailed explanation of this specification, a frequency of 20-50 KHz, and an intensity of 100-500 mW/cm2 is disclosed, but there is no disclosure of any scientific reason why these values are specified, nor any scientific data explaining what the specified values are based on. Further, no commercialized product has yet appeared on the market.
The specified values 20-50 KHz at 100-500 mW/cm2 and 1-3 MHz at 100-500 mW/cm2 in the prior art, do not have any scientifically provable data attesting to their effectiveness. Further, the reasons why these values are specified, taking safety into consideration, have not been described. According to the experiments carried out and described later by the inventor, these values are inadequate.
An object of the present invention is to clarify the effective frequency and intensity, including safety considerations, for lipolysis of living bodies, as well as providing equipment for performing lipolysis of a living body safely and effectively using ultrasound sonication.
In a living body, fat is synthesized by lipo-synthesizing enzymes in the adipocyte from glucose and free fat acid, and forms an oil droplet. As for humans, adipocyte of adults is mostly white adipocyte. So, hereafter, adipocyte shall be taken to imply white adipocyte. Adipocyte is slender and 20 xcexcm in length at birth but grows to a 100 xcexcm (sometimes 200 xcexcm) diameter sphere in accordance with fat accumulation.
The accumulation of fat in adults is caused by the growth of each adipocyte rather than an increase in their number. In a grown adipocyte, the oil droplet is covered by a water based cell liquid layer, the thickness of which is much less than the diameter of the oil droplet itself.
In the cell liquid, there is enclosed an endoplasmic reticulum, which includes a lipolytic enzyme referred to as hormone sensitive lipase (HSL), which decomposes the fat into glycerol and fatty acid. Meanwhile., the fat oil droplet surface is covered with a flowable molecular layer of phospholipid and is protected from contact with the lipolytic enzyme located on the endoplasmic reticulum surface.
In the fat of the living body, the phospholipid layer partly disappears when hormones, such as epinephrine (adrenaline) released from adorenal modula or norepinephrine (noradorenarine) released from sympathetic nerve, are introduced. Then the oil drop makes contact directly with the endoplasmic reticulum and lipolysis starts. Fat is resolved into glycerol and free fatty acid, and the resolved products exit from the cell into the blood and are finally burned or consumed by exercise etc. The remaining final products are discharged from the body as CO2 and H2O in expiration and/or urine.
It is known that ultrasound sonication on a living body has effects such as the promotion of enzyme reactions, emulsification, thermogenic effects, expansion of capillary blood vessels, and enhancement of metabolism. In the present invention, the increase of peripheral blood flow by expansion of the capillary blood vessels as a result of sonication is the same as in the prior art equipment used for health and beauty. However, the inventors have doubts about the lack of scientific evidence for the effectiveness of such conventional equipment for health and beauty and the frequencies used for them. As predicted from the aforesaid biochemical mechanisms of lipolysis, there must be an effective frequency less than 1 MHz, and the effectiveness must be frequency dependent, for such mechanisms as the stimulation of sympathetic nerves, the release of hormones at their ends, and activation and fluidization of the phospholipid layer. The inventors have confirmed the effective frequency and its intensity experimentally to examine this prediction. The present invention is based on the fact that the results obtained by such experimentation are quite different from the descriptions in the prior art.
According to the invention, a reasonable explication is as follows. The end of the sympathetic nerve is stimulated by sonication at a specific frequency and intensity which releases a hormone for lipolysis such as norepinephrine (noradorenarine), or the phospholipid layer or oil drop itself may be agitated and some contact occurs between the oil drop and the endoplasmic reticulum, namely a lipolysis enzyme, and thus, lipolysis occurs.
A first aspect of the present invention is an ultrasound sonication equipment, providing an ultrasound generation means for treating a living body with the generated ultrasound to thereby cause lipolysis of fat in the living body, specifically characterized by an ultrasound energy of 15-140 KHz, and wherein the intensity at the sonicated body surface is greater than 10 mW/cm2 and below the hemolysis safety limit when the ultrasound energy is between 15-50 kHz, and greater than 4 mW/cm2 and less than the hemolysis limit or the safety limit defined by the Mechanical Index when the ultrasound energy is between 50-140 kHz.
A second aspect of the present invention is an ultrasound sonication equipment, providing an ultrasound generation means for treating a living body with the generated ultrasound to thereby cause lipolysis of fat in the living body, specifically characterized by an ultrasound energy of 180 KHz-1.3MHz, and wherein the intensity at the sonicated body surface is greater than 10 mW/cm and below the safety limit defined by the Mechanical Index when the ultrasound energy is between 180-700 kHz, and is greater than 800 mW/cm2 and below the safety limit defined by the Mechanical Index when the ultrasound energy is between 700 kHz-1.3 Mhz.
In the ultrasound sonication equipment according to the first and second aspects, the allowable maximum intensity is set below the level of no hemolysis or the safety level of Mechanical Index, but preferably is set below the level of no hemolysis or the safety level for medical diagnostic equipment.
Further, the equipments according to the first and second aspects are characterized by an intensity safety level which is set depending on the frequency for the Mechanical Index (MI): MI=0.6. The sonication can be any of continuous, pulsed, or intermittently generated, or a combination of such sonications. Intermittent sonication can be used to separate the time for forming the contact of the oil droplet with an enzyme, from the time in which fat is resolved after such contact.
Meanwhile, from a view point of health, it is not desirable for sonication to be performed carelessly. The safety level for medical diagnostic equipment is set at 1000 mW/cm2 in the standard of the Society for Ultrasound in medicine and Biology, and by the FDA in the U.S.A., and this value can be described as applicable for a frequency range of 1-10 MHz. In this region, the intensity attenuation with penetration through the living body is strong, and the effective depth is limited to a shallow region beneath the body surface.
Here, the xe2x80x9ceffective depth is defined as the depth from the body surface, where lipolysis occurs effectively by sonication.
The energy given to the body is proportional to the intensity and time of the sonication. Penetration intensity decreases following an exponential function with the penetrated path length, where the exponent is given by a product of an absorption coefficient x length. Further, the absorption coefficient in the living body is proportional to the applied frequency. For example, the absorption coefficient divided by the frequency in human fat is 0.063 neper/cmMHz. So, the attenuation/absorption coefficient for penetration of 1 cm of fat is 0.55 dB/cm for 1 MHz and 1.09 dB/cm for muscle.
According to the inventor experiments, the effective intensity range for lipolysis was as wide as 10-1000 mW/cm2 at a frequency of 500 kHz. And its effectiveness was constant for the widely spread intensity ranges. The effective depth can be calculated from the data as 135 cm for fat and 70 cm for muscle. In other words, the aforesaid intensity of 500 kHz can cause lipolysis still at deep viscera fat even after being attenuated to as low as 10 mW/cm2, but such a low intensity never produces effects on bone and viscera.
On the other hand, the effective depth at 1 MHz is calculated as 1.7 cm for fat and 0.9 cm for muscle from the effective range of 800-1000 mW/cm2, obtained by the experiment.
Again, the World Federation for Ultrasound in Medicine and Biology (WFUMB) introduced a concept of a Mechanical Index (MI) to estimate the risk of tissue destruction due to the mechanical cavitation. The MI is given by the following equation MI=P/fxc2xd, wherein P is the maximum negative peak pressure in units of Mpa, and f is frequency in units of MHz.
The allowable level of the MI is not clearly defined and is left to the medical doctor discretion while compromising benefit and risk. However, some descriptions in which MI=0.6 or less are seen in medical treatment as safe. The Japanese Society for Ultrasound in Medicine has defined that MI should be less than 1. The present inventors have employed MI=0.6 as a limit, even though the limit may be altered in the future. This level can be applied for persons suffering from diseases of obesity and diseases whose origins lie in obesity. For undefined healthy individuals seeking applications for health and beauty enhancement, a level for medical diagnostic application of 1000 mW/cm2 is recommended.
At a frequency of less than 1 MHz which is to be expected for biochemical fat reduction, ultrasound energy has strong penetration ability as well as a strong biochemical reaction. So, the influence on bone, blood vessel and viscera must be carefully considered.
Especially, in a range less than 100 kHz, dominant cavitation may pose a risk of tissue destruction and some stick tick feeling, even in the safer lower region, can be felt as uncomfortable. Further, hemolysis is easily produced by large emulsifying or dispersion forces. These actions are also functions of frequency and intensity. So, the intensity level should be below the aforesaid hemolysis limit.
Further, the FUMB noticed that care should be taken in regards to the tissue temperature under sonication, including such wider applications as medical treatment due to a thermal heating effect of sonication, and introduced the concept of s Thermal Index (TI) as a measure of the rise in temperature caused by sonication. A temperature elevation of less than 1.5xc2x0 C. (TI less than 1.5) is quite safe in long term sonication, whereas 2xc2x0 C. for 30 min. or 4xc2x0 C. for 5 min. must be used under great caution.
Accordingly, the equipment according to the present invention includes a monitoring means for monitoring the location and temperature of the part of the body undergoing sonication. The ultrasound sonication equipment according to the invention provides a monitoring means which can perform such functions as determining the internal structure of the part of the body undergoing sonication, confirming the area undergoing sonication, determining an intensity level, calculating a time-integrated sonicated amount, and monitoring of the temperature rise caused by such sonication. Thus, it is possible to perform sonication while monitoring temperature elevation, while focusing on a specific viscerum and its vicinity, and avoiding exposing specific bones or viscerum to sonication. Hence, a safe and effective sonication can be realized.
In the ultrasound sonication equipment of the present invention, a sound energy transmitting means (applicator) is provided which generates ultrasound by the aforesaid means through an acoustic conducting medium. As such a medium, water, a bag containing water or liquid inside, and a non-liquid sound coupler etc., can be used. As the applicator (sound energy transmitting means), a bath or water box having the aforesaid ultrasound generator therein and a sound conducting medium like water, or a probe-like ultrasound applicator having the aforesaid ultrasound generator and a sound conducting bag containing a medium such as water or a non-liquid sound coupler etc. can be used. In the ultrasound sonication equipment of the present invention, the aforesaid ultrasound applicator provides an acoustic coupling layer between the applicator and the surface of the body. If an air layer exists between the applicator and the body surface, ultrasound is reflected by the air layer and cannot enter into the body. Therefore, interposing a coupling agent between the applicator and the body surface is used to avoid loss due to reflection and secures a positive sonication on the body. Such a coupling agent can be of any substance which acts to exclude air, such as a jelly or cream.
The coupling agent can also contain obesity reducing substances. By mixing percutaneous ointment with the coupling agent, or using the ointment itself as the coupling agent, a substance combining obesity reduction and acoustic coupling can be offered. Such combinations offer synergistic effects on fat reduction.
As a further aspect, the sound applicator can be one which provides a water flow for carrying ultrasound onto the surface of the body. For example, a shower head containing an ultrasound generator therein and which provides water or flows of warm water jets onto the body can be used, thereby generating the water flow jets carrying ultrasound therein, and used for sonication on the body. In another example, explained hereafter, the ultrasound generator is equipped in a bath and the warm water flow carrying ultrasound therein is generated and circulated in the bath. Then, the flow delivers ultrasound to the body. These examples disclose such applicators for a comfortable, labor free and easily operable sonication.
The substances which are decomposed by the aforesaid procedures, such as FFA, are released into the blood. It is necessary to burn or consume them by exercise or elevation of body temperature because, otherwise, they will be synthesized again into fat.
Therefore, in the present invention, the equipment can provide an obesity reducing agent together with the aforesaid sonication. Such an agent can be of percutaneous or oral administration, or can be administered by injection. For example, a food such as mustard, or medicines such as capsaicin, capsaicinoids or sibutramine, which elevate one""s body temperature and enhance thermogenesis, can be taken or administered. Such a rise in body temperature, in the long term, tends to increase thermal radiation towards the outside of the body and thereby enhances the burning of FFA, etc.
Thereby, a synergistic effect, such as localized fat reduction, can be obtained by the combination of sonication and administration of the aforesaid obesity reduction agents. The combination can prevent fat from shifting from other parts of the body to the site which has been sonicated and reduced in fat.
The ultrasound sonication equipment of the present invention can provide a cooling means to cool at least a part of the body. If a part of the body is cooled, thermal energy is removed and a thermogenetic function due to homeostasis of the living body works autonomically to keep one""s body temperature constant by the consumption or burning of FFA.
Such cooling means can comprise the aforementioned sound conducting medium, which has been cooled and prepared for contact with the body. If a controlling means to keep the temperature of the aforesaid sound conducting medium is kept at a temperature 24xc2x0 C. cooler than body temperature, the body""s own thermal energy is taken away, since any homeothermal animal generates autonomic thermogenesis.